In the rather brief period since Rett syndrome (RS) came to international attention in 1983, remarkable progress has been achieved in our understanding of this puzzling disorder. The clinical pattern and spectrum of RS has been defined with greater specificity. In particular, a more systematic scheme has been developed to validate the variant clinical presentations. In the absence of a consistent metabolic or neurochemical abnormality, greater attention has been devoted to morphologic and neurobiologic studies. These analyses suggest a fundamental failure in neurodevelopment with respect to neuronal maturation and dendritic arborizations essential for cell-cell connectivity.
